PO.PR02.01 · 预防研究
腊肠树（Cassia fistula L.）树皮氯仿部位的脂质体包封增强了在艾氏腹水癌小鼠模型中的抗癌疗效
Liposomes encapsulated chloroform fraction of Cassia fistula L. bark enhances anticancer efficacy in ehrlich ascites carcinoma mice model
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
癌症仍是全球死亡的主要原因之一，也是深刻影响世界范围内预期寿命的重大健康问题。腊肠树（Cassia fistula L.），俗称“金链花”，在阿育吠陀医学和中国传统医学中均有应用。采用极性递增的有机溶剂从树皮粉末中提取植物成分，即CaMH（正己烷部位）、CaMC（氯仿部位）、CaME（乙酸乙酯部位）和CaMM（甲醇部位）。采用MTT法在HeLa（宫颈癌）、MCF-7（乳腺癌）、LN-18（脑胶质母细胞瘤）、MG-63（骨肉瘤）、A431（皮肤癌）、MIA PaCa-2（胰腺癌）以及正常细胞系L929（人成纤维细胞）中检测了这些树皮部位的细胞毒性潜力。在所有被检测的部位中，CaMC部位对HeLa细胞表现出最高的选择性细胞毒性，GI50值为41.53 μg/mL。对CaMC部位进行硅胶柱层析得到Cf-1部位，经光谱学鉴定为胡椒碱（Piperine）。其对HeLa、MG-63和MCF-7细胞系表现出显著的细胞毒性，GI50分别为0.10 mM、0.37 mM、0.56 mM。经CaMC和Cf-1部位处理的HeLa细胞在形态学和流式细胞术检测中显示出明显的凋亡表现。这些部位以浓度依赖方式诱导细胞周期阻滞于G0/G1期。CaMC和Cf-1部位的分子机制研究表明，凋亡标志物（包括p53、caspase 3和9）上调，Bcl-2下调。此外，在荷艾氏腹水癌的瑞士白化小鼠中进行的体内研究显示，脂质体包封的CaMC部位（CaMC-LP）实现了82.23%的肿瘤生长抑制，而CaMC部位为60.81%的肿瘤抑制，与5-氟尿嘧啶的86.39%抑制相当。脂质体包封的使用在体外增强了抗癌疗效，在体内对荷EAC小鼠表现出显著的肿瘤抑制且未引起毒性。这些发现提示，腊肠树树皮成分具有癌症化学预防和化学治疗潜力，可进一步开发以造福人类。
查看英文原文 English abstract
Cancer remains one of the eminent causes of mortality and a major health concern profoundly influencing life expectancy worldwide. Cassia fistula L. commonly known as ‘Golden shower' finds its application in the Ayurveda and Chinese traditional medicines. The phytoconstituents from the bark powder were obtained using organic solvents in the increasing order of polarity viz. CaMH (hexane fraction), CaMC (chloroform fraction), CaME (ethyl acetate fraction) and CaMM (methanol fraction). These bark fractions were tested for their cytotoxic potential in HeLa (cervical cancer), MCF-7 (breast cancer), LN-18 (brain glioblastoma), MG-63 (osteosarcoma), A431 (skin cancer), MIA PaCa-2 (pancreatic cancer) and normal cell line L929 (human fibroblast cells) using MTT assay. Among all the tested fractions, CaMC fraction shows highest selective cytotoxicity against HeLa cells with GI 50 value of 41.53 µg/mL. Silica gel column chromatography of CaMC fraction yielded Cf-1 fraction spectroscopically deciphered as Piperine. It showed significant cytotoxicity against HeLa, MG-63 and MCF-7 cell line with GI 50 of 0.10 mM, 0.37mM, 0.56 mM respectively. CaMC and Cf-1 fractions treated HeLa cells showed significant manifestations of apoptosis in morphological and flow cytometric investigations. These induced cell cycle arrest at G 0 /G 1 phase in concentration-dependent manner. Molecular mechanistic studies of CaMC and Cf-1 fraction depicted upregulation of apoptotic markers including p53, caspase 3 and 9, and downregulation of Bcl-2. Furthermore, the in-vivo studies evaluated in Ehrlich Ascites Carcinoma-bearing Swiss albino mice showed that liposomal encapsulated CaMC fraction ( CaMC-LP ) resulted in 82.23% tumor growth inhibition in contrast to CaMC fraction with 60.81% tumor inhibition, comparable to 86.39% inhibition by 5-Fluorouracil. The use of liposomal encapsulation enhanced the anticancer efficacy in vitro, and in vivo showing significant tumor inhibition in EAC- bearing mice without inducing toxicity. These findings suggest that C. fistula L. bark constituents have cancer chemopreventive and chemotherapeutic potential which can further be exploited for the benefit of mankind.
利益披露 Disclosure
S. Kaur, None..
R. Kour, None.